Epstein-Barr virus is seldom the causative agent of a prolonged atypical illness, known as chronic mononucleosis syndrome, characterized by a persistent pattern of clinical manifestations and by a defective immune response to specific viral antigens. This paper refers about 6 children for whom clinical and serological findings suggest the chronic Epstein-Barr virus infection. The authors believe that this chronic state might be explained by the unusual antibody pattern to EBV virus, with the persistent presence of anti-EA and the absence of anti-EBNA titers, expression of a reduced EBV-specific cytotoxic T cell activity.